This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Aims and Results Massive growth of reactive astrocytes after focal brain injury suggests critical roles of this cell type in the progress of tissue degeneration and/or recovery. However, basic questions about postlesional reactive astrocytes, such as "Are reactive astrocytes neuroprotective or neurodegenerative?" and "Do reactive astrocytes promote or inhibit neuronal network regeneration?" are still to be addressed. The current confusion in postlesional reactive astrocyte studies is largely attributed to the lack of appropriate animal model. The gliosis in existing focal brain injury models are likely complicated by an experimental artifact. A recent publication reported that the large craniotomy, which is commonly used in brain injury models for creating focal and severe injury in small rodent brains, caused gliosis by itself (Xu et al, Nature Neuroscei. 2007). Thus, the reactive astrocytes, which are well recognized as heterogeneous cell population, in existing brain injury models reflect experimental artifacts, rather than clinically-relevant pathological processes. In order to overcome this problem, we established a novel brain injury model for studying functions of postlesional reactive astrocyte without the artifactual gliosis in Year 1. For this purpose, we created focal brain injury by the intense light exposure through thinned-skull cranial window, which did not cause the artifactual gliosis. Small skull region, which was large enough for focusing light in cortical tissue through 20x microscope objective (approximately 0.5 mm in diameter), was scraped for increasing light transmittance. By exposing cortical tissue to light from 90W halogen lamp, we successfully created severe brain injury in mouse somatosensory cortex in closed-head condition.